title: Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training.
abstract: The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. The present study investigated the mRNA regulation of components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), muscle enriched miRNAs, (miR-1, -133a, -133b and -206), and several miRNAs dysregulated in muscle myopathies (miR-9, -23, -29, -31 and -181). Measurements were made in muscle biopsies from nine healthy untrained males at rest, 3 h following an acute bout of moderate-intensity endurance cycling and following 10 days of endurance training. Bioinformatics analysis was used to predict potential miRNA targets. In the 3 h period following the acute exercise bout, Drosha, Dicer and Exportin-5, as well as miR-1, -133a, -133-b and -181a were all increased. In contrast miR-9, -23a, -23b and -31 were decreased. Short-term training increased miR-1 and -29b, while miR-31 remained decreased. Negative correlations were observed between miR-9 and HDAC4 protein (r=-0.71; P=0.04), miR-31 and HDAC4 protein (r=-0.87; P=0.026) and miR-31 and NRF1 protein (r=-0.77; P=0.01) 3 h following exercise. miR-31 binding to the HDAC4 and NRF1 3 untranslated region (UTR) reduced luciferase reporter activity. Exercise rapidly and transiently regulates several miRNA species in muscle. Several of these miRNAs may be involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis. Identifying endurance exercise-mediated stress signals regulating skeletal muscle miRNAs, as well as validating their targets and regulatory pathways post exercise, will advance our understanding of their potential role/s in human health.
authors.affiliation: A. P. Russell: Centre for Physical Activity and Nutrition Research (C-PAN), School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway 3125, Burwood, Australia. aaron.russell@deakin.edu.au.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Russell
authors.forename: Severine
authors.initials: S
authors.lastname: Lamon
authors.forename: Hanneke
authors.initials: H
authors.lastname: Boon
authors.forename: Shogo
authors.initials: S
authors.lastname: Wada
authors.forename: Isabelle
authors.initials: I
authors.lastname: Güller
authors.forename: Erin L
authors.initials: EL
authors.lastname: Brown
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Chibalin
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
authors.forename: Rod J
authors.initials: RJ
authors.lastname: Snow
authors.forename: Nigel
authors.initials: N
authors.lastname: Stepto
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Wadley
authors.forename: Takayuki
authors.initials: T
authors.lastname: Akimoto
mesh_terms: D000328:Adult; D019295:Computational Biology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D015444:Exercise; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism; D010807:Physical Endurance; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism
chemical_list: D028884:Karyopherins; D035683:MicroRNAs; C495633:NRF1 protein, human; D051266:Nuclear Respiratory Factor 1; D012097:Repressor Proteins; C446511:XPO5 protein, human; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; C400300:HDAC4 protein, human; D006655:Histone Deacetylases; D053487:DEAD-box RNA Helicases